1. Field of the Invention
The present invention relates to a composition for use in producing neural stem cells from fibroblasts. In particular, it relates to a synthetic peptide capable of inducing differentiation of fibroblasts into neural stem cells, or in other words to a synthetic peptide for use in the aforementioned composition. It also relates to a method for producing neural stem cells from fibroblasts using this synthetic peptide (or composition).
The priority claim for this application is based on Japanese Patent Application No. 2015-191658 submitted on Sep. 29, 2015, and the entire contents of that application are incorporated herein by reference.
2. Description of the Related Art
One issue in the field of regenerative medicine is the regeneration and restoration of neural function lost due to various kinds of neurological disease, injury and the like.
For example, methods are being explored of transferring nerve cells produced by in vitro culture into an affected area to replace lost nerve cells. However, even when nerve cells that have already undergone axon elongation are transferred into an affected area (into central nervous system tissue such as brain, for example), it can be difficult to reconstruct the neural network before the injury. In particular, because central nervous system tissue achieves and maintains neural function by constructing a physiological environment involving interactions between nerve cells and various other cells (such as astrocytes), it can be difficult to restore neural function by replenishing only the nerve cells.
Techniques for regenerating and restoring neural function using neural stem cells are therefore much anticipated. For example, it is hoped that methods can be developed of restoring neural function by introducing neural stem cells into an affected area (into central nervous system tissue such as brain, for example) or using the regenerative ability of endogenous neural stem cells, and inducing these to differentiate into the necessary cells (such as nerve cells or astrocytes) in vivo (typically in an affected area) to thereby replace lost cells and reconstruct the neural network and physiological environment.
Methods of obtaining neural stem cells that can be transferred into affected areas include isolating the cells from brain tissue, or inducing them from embryonic stem (ES) cells, induced pluripotent stem (iPS) cells and other pluripotent stem cells. However, methods using neural stem cells in the brain and methods of inducing neural stem cells from ES cells are difficult to implement due to ethical issues and problems of rejection and the like. Moreover, methods of inducing neural stem cells from iPS cells still face practical issues of safety, efficiency and cost.
In recent years, therefore, attention has focused on the development of so-called “direct reprogramming” techniques, in which target cells (such as neural stem cells) are prepared directly from somatic cells without an intermediate step of preparing pluripotent stem cells (such as iPS cells). For example, Japanese Translation of PCT Application No. 2013-535973, Nature 463, 2010, pp. 1035-1041 and Nature 476, 2011, pp. 220-223 all describe techniques for transdifferentiating (fate transforming) somatic cells into neural stem cells (or nerve cells) by introducing specific genes into the somatic cells, or in other words techniques of direct reprogramming neural stem cells (or nerve cells) from somatic cells.